OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

BACKGROUND:Maxillofacial bone three-dimensional(3D)printing technology has been widely used in clinical diagnosis and treatment,but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data.The lens,thyroid and other parts of the human body are extremely sensitive to X-rays;therefore,it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.OBJECTIVE:To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing.METHODS:The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group(conventional CT-dose,120 kVp,automated tube current modulation,n=32)and a low-CT-dose 3D printing group(low-CT-dose group,80 kVp,automated tube current modulation,n=33).The effective dose of radiation was calculated and compared between the two groups.A Likert scale was used to evaluate the quality of 3D printing in the two groups,and the measurement bias and consistency between evaluators were measured using the Bland-Altman method.RESULTS AND CONCLUSION:(1)There was no significant difference in the general demographic characteristics(age,height,weight,body mass,sex,and body mass index)between the two groups(all P＞0.05).(2)The effective dose value of the low CT-dose 3D printing group was(0.3±0.1)mSv,which was about 62.5％lower than that in the conventional CT-dose 3D printing group[(0.8±0.1)mSv].(3)There was no significant difference in the subjective scoring of 3D printing quality between the two groups(all P＞0.05).The subjective consistency among evaluators was good,with Kappa values of 0.85,0.80,and 0.76.The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line,indicating good consistency between the two groups.To conclude,low-dose CT technology can be effectively applied in maxillofacial bone 3D printing,reducing radiation dose without affecting the quality of 3D printing.

BACKGROUND:Maxillofacial bone three-dimensional(3D)printing technology has been widely used in clinical diagnosis and treatment,but the data source before performing maxillofacial bone 3D printing mainly comes from the CT scanning data.The lens,thyroid and other parts of the human body are extremely sensitive to X-rays;therefore,it is particularly important to effectively reduce the dose of CT radiation when acquiring the data source.OBJECTIVE:To explore the feasibility of low-dose CT technology in optimizing radiation dose for maxillofacial bone 3D printing.METHODS:The medical records of 65 patients who underwent maxillofacial bone 3D printing in the Department of Stomatology at the General Hospital of Northern Theater Command from March 2021 to December 2023 were retrospectively collected and categorized into a conventional CT-dose 3D printing group(conventional CT-dose,120 kVp,automated tube current modulation,n=32)and a low-CT-dose 3D printing group(low-CT-dose group,80 kVp,automated tube current modulation,n=33).The effective dose of radiation was calculated and compared between the two groups.A Likert scale was used to evaluate the quality of 3D printing in the two groups,and the measurement bias and consistency between evaluators were measured using the Bland-Altman method.RESULTS AND CONCLUSION:(1)There was no significant difference in the general demographic characteristics(age,height,weight,body mass,sex,and body mass index)between the two groups(all P＞0.05).(2)The effective dose value of the low CT-dose 3D printing group was(0.3±0.1)mSv,which was about 62.5％lower than that in the conventional CT-dose 3D printing group[(0.8±0.1)mSv].(3)There was no significant difference in the subjective scoring of 3D printing quality between the two groups(all P＞0.05).The subjective consistency among evaluators was good,with Kappa values of 0.85,0.80,and 0.76.The scatter points in the Bland-Altman for both protocols were uniformly distributed within the standard deviation line,indicating good consistency between the two groups.To conclude,low-dose CT technology can be effectively applied in maxillofacial bone 3D printing,reducing radiation dose without affecting the quality of 3D printing.

Solid-phase extraction(SPE)combined with surface-enhanced Raman spectroscopy(SERS)has emerged as a promising analytical technique for detection and analysis of trace components in complex sample matrices.SPE enriches analytes through selective adsorption and solvent elution,effectively increasing the concentration and signal intensity.SERS enables ultra-sensitive and highly selective molecular analysis through the use of SERS-active substrates engineered to amplify Raman signals.The integration of these two techniques overcomes the limitations of conventional Raman spectroscopy in low-concentration detection field,while significantly improving sample preparation efficiency and analytical accuracy.This review provided a comprehensive overview of the characteristics of three SPE-SERS coupling modes,including two-step,one-step,and online integration.Special emphasis was placed on recent advancements in one-step SPE-SERS approaches based on novel functional adsorbent materials such as graphene,metal-organic frameworks,covalent organic frameworks,and molecularly imprinted polymers.Furthermore,future directions and development prospects of SPE-SERS technology were discussed.

Objective : To explore the utility of a nomogram integrating contrast-enhanced CT radiomics with clinical features in the preoperative prediction of WHO/ISUP grade for clear cell renal cell carcinoma(ccRCC). Methods: A total of 214 patients with pathologically proven ccRCC who underwent enhanced CT scan before surgery were retrospectively included. According to the WHO/ISUP grade system, the cases were classified into low-grade(grades Ⅰ-Ⅱ) and high-grade(grades Ⅲ-Ⅳ), and then randomly divided into training and test set with a ratio of 4 ∶1. Regions of interest were segmented from both unenhanced and three-phase enhanced images, and radiomic features were extracted. Feature selection and dimensionality reduction were performed using Spearman rank correlation coefficients and LASSO regression, followed by the construction of the radiomic model with the KNN algorithm. Clinical and semantic imaging features were selected through univariate and multivariate analyses, and a clinical model was developed using the KNN algorithm. The clinical and radiomics signatures were used to construct a combined model and a nomogram was developed. The ROC curve and delong test were used to evaluate the diagnostic performance of the model, while calibration and decision curve analyses assessed its accuracy and clinical applicability. Results: 8 clinical features and 11 radiomic features were selected. The combined model, integrating these clinical and radiomics signatures, exhibited robust predictive performance with AUC values of 0.887 in the training set and 0.800 in the test set. The calibration curve demonstrated good consistency between the nomogram model and actual outcomes, while decision curve analysis indicated a favorable net benefit for the nomogram. Conclusion The nomogram constructed by combining radiomics and clinical signatures can provide evidence for preoperative prediction of ccRCC grade and guide clinical decision-making.

The surgical treatment of thoraco-abdominal aortic aneurysm (TAAA) requires a unique multidisciplinary approach. A thorough preoperative examination and evaluation are essential to determine the optimal timing for surgery and to optimize organ function as needed. During the perioperative period, excellent surgical skills and an appropriate strategy for extracorporeal circulation will be employed based on the extent of the aneurysm. Additionally, necessary measures will be taken to monitor and protect the functions of vital organs. Close monitoring and management in the postoperative stage, along with early detection of complications and effective treatment, are crucial for improving the prognosis of TAAA surgery. This article reviews the current research progress in the perioperative management of TAAA surgery.

Objective To investigate the effect of community management model on elderly patients with non-valvular atrial fibrillation(NVAF),and to provide methods and ideas for the management of elderly patients with NVAF in community.Methods A prospective randomized controlled trial was conducted in 305 elderly patients with NVAF who visited two community health service centers in Hefei and Wuhu from De-cember 2022 to November 2023.The patients were randomly divided into the control group(n=152)and the experimental group(n=153)by random number table method.The control group received routine diagnosis and treatment measures,while the experimental group adopted the community management model.Both groups were treated for 6 months.The New York Heart Association(NYHA)cardiac function classification was used to evaluate patients'cardiac function,the European Heart Rhythm Association(EHRA)score was used to assess patients,atrial fibrillation symptoms,the Morisky Medication Adherence Scale(MMAS-8)was used to evaluate patients'medication adherence,and the general self-efficacy scale(GSES)was used to assess patients'self-efficacy.The ventricular rate,control of cardiovascular risk factors,use rate of anticoagulant drugs,and the incidence of bleeding and arterial embolism were recorded in both groups.Results After 6 months of intervention,the NYHA cardiac function classification,EHRA score and ventricular rate control in the experimental group were better than those in the control group,and the patients'MMAS-8 and GSES scores were higher.The compliance rate of blood pressure and fasting blood glucose,and the use rate of antico-agulant drugs in the experimental group were higher than those in the control group.There was no statistical-ly significant difference in the incidence of bleeding and arterial embolism between the two groups(P>0.05).Conclusion The community management model can improve the symptoms,cardiac function,use rate of anticoagulant drugs,and medication adherence of elderly NVAF patients,and enhance their quality of life.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*